Introduction

Background
Although rare in developed countries, brain abscess is a serious, life-threatening emergency.
Once having a dire outcome, morbidity and mortality have decreased because of advances in
diagnostic modalities, antibiotic regimens, and earlier surgical interventions.1,2However, changes
in epidemiology, including new disease pathogens and predisposing factors, have renewed
concern about the diagnosis and treatment of this condition.

Pathophysiology
Brain abscess is a focal infection, which begins when organisms are inoculated into the brain
parenchyma, usually from a site distant from the central nervous system (CNS). Abscess
formation occurs through several stages. Inflammation during the "early cerebritis" stage evolves
into a necrotic collection of pus, eventually surrounded by a well-vascularized capsule after 2
weeks.3,4

The 3 mechanisms of entry into the brain are as follows:2,5,6

• Direct extension: Infections stemming from the sinuses, teeth, middle ear, or mastoid
may gain access to the venous drainage of the brain via valveless emissary veins that
drain these regions. Because of improved antibiotic therapy for ear infections, this
mechanism is decreasing in incidence, accounting for only approximately 12-25% of
cases.2,7 However, in developing countries, this is still a significant source accounting for
at least 50% of cases.8
• Hematogenous: Seeding of the brain occurs from distant infection sites and often results
in multiple brain abscesses.9 This remains an important cause of brain abscess.
• Following penetrating head injury or neurosurgery: Previously low in incidence, more
brain abscesses are developing after head trauma and neurosurgical procedures. A case
series found that 37% of brain abscesses were associated with head penetration.2,10

Up to 30% of abscesses are cryptogenic and have no clear source.2,8,9

Frequency
United States

Brain abscess is rare in the general population; however, immunocompromised patients have
increasing incidence of brain abscess, often with fungal or protozoan organisms.

In the United States, 1500-2500 cases are reported per year.9

Mortality/Morbidity

• The mortality rate from brain abscess is currently approximately 10%.1,2,8,11,12

• However, if the abscess ruptures into the ventricular system, the mortality rate may be
80%.2
• Morbidity in survivors is generally due to residual neurologic defects, increased incidence
of seizures due to scar tissue foci, or neuropsychiatric changes.9
Race
No compelling evidence exists for racial differences in the incidence of brain abscess.

Sex
Brain abscess occurs two to four times as often among men than women.2,4,7,8,13,14

Age
Traditionally, brain abscesses were disproportionately diagnosed in the young. However, with
changes in vaccination practices, treatment of pediatric infections, and the AIDS pandemic,
current literature suggests a shift in peak incidence toward the third to fifth decades of life.2,14,15 The
minority of abscesses that do occur in children peak in the age range of 4-7 years.16

Clinical

History

• Headache is the most common presenting symptom of brain abscess (50-90% of

cases).2,7,14
• Focal neurologic deficit (50%) may correlate with the local region of infection.6,7
• Classic triad of headache, fever, and focal neurologic deficit is rarely seen (<5-20% of
cases in case series).2,8
• Seizure (40%) and mental status changes (50%) are common.2,14
• Nausea, vomiting, or stiff neck may be reported with increased cerebral edema due to the
mass lesion.6,8
• Sudden worsening of a preexisting headache accompanied with meningismus may be
indicative of a catastrophic event—rupture of the abscess into the ventricular space.6

Physical

• Fever is typically low grade, but presence or absence of fever does not aid in diagnosis,
as it is present in less than half of all cases.6,14
• Altered mental status ranges from subtle personality changes through drowsiness to full-
blown coma.14
• Nuchal rigidity occurs in about 25% of cases.14
• Focal neurologic findings are commonly present6,14 and can signal increasing cerebral
edema around the abscess.4
• Seizures are typically generalized.14
• Papilledema indicates the disease process is well advanced and increased intracranial
pressure is present.14
• Bulging fontanelles, irritability, and enlarging head circumference may be noted in
infants.5

Causes
A wide variety of organisms can cause brain abscess, depending on the portal of entry, and up to
one third may be polymicrobial.3,6
 • Direct extension - Sinus, odontogenic, and otogenic sources are common.
o Streptococcus species (aerobic and anaerobic) are most frequently isolated.
o Other organisms include Bacteroides, Enterobacteriaceae, Pseudomonas,
Fusobacterium, Prevotella, Peptococcus, and Propionibacterium.
• Hematogenous spread - Pathogens depend on predisposing source. Some common
examples are listed below.
o Endocarditis -Streptococcus viridans, Staphylococcus aureus
o Pulmonary infections -Streptococcus, Fusobacterium,
Corynebacterium, and Peptococcus species
o Cardiac defects with right-to-left shunt -Streptococcus species
o Intra-abdominal infections -Klebsiella species, E coli, other
Enterobacteriaceae, Streptococcusspecies, anaerobes
o Urinary tract infections - Enterobacteriaceae, Pseudomonas species
o Wound infection -S aureus
• Penetrating head trauma, postoperative10
o S aureus is most commonly isolated.
o Enterobacteriaceae, other gram-negative bacilli, S
epidermidis, Clostridium species, anaerobes, andPseudomonas species may
also be found.
o Propionibacterium acnes, an indolent gram-positive anaerobic organism, may
cause delayed postoperative brain abscess, even 10 years after an intracranial
procedure.17
• Rarely, cases of brain abscess have been reported even after nonpenetrating traumatic
intracranial hemorrhage.18
• Opportunistic infection is an increasing cause of brain abscess, as there are more
patients with organ transplant, HIV, and immunodeficiencies. Common organisms
include Toxoplasma gondii and Nocardia, Aspergillus, and Candida species.4,5,6 Cases
of Nocardia are increasing even in immunocompetent patients and have high
mortality.2,4,19
• Other predisposing risk factors include intravenous drug use, cardiac abnormalities (ie,
prosthetic valve, septal defect), cyanotic congenital heart disease (most common cause
of multiple brain abscesses in children), diabetes, chronic steroid use, alcoholism, and
neoplasm.2,9,14
• Case reports of near drowning, foreign body aspiration, application of dental braces,
tongue piercing, and upper endoscopic procedures such as esophageal dilatation and
variceal ligation have also been associated with brain abscess.20,21,22,23,24,25
• When there is no obvious source (up to 25% of cases), upper respiratory tract flora and
anaerobes are often isolated.2 Several sources have identified a patent foramen ovale by
echocardiogram in these cases and propose this as a possible mechanism for seeding
oral flora to the brain.26
• Several cases of community-acquired methicillin-resistant Staphylococcus aureus (CA-
MRSA) causing brain abscess have been reported recently, so this must be considered
when initiating empiric therapy in patients presenting with neurologic symptoms who also
have risk factors for CA-MRSA.

Workup

Laboratory Studies
Laboratory tests are rarely helpful in establishing a diagnosis of brain abscess.2,9

• Elevated white blood cell (WBC) count or erythrocyte sedimentation rate (ESR) is not
reliably found.6,30
• Blood culture results may only be positive in 30% of patients2,31 but should always be
obtained. Hematogenous spread may be the source as noted above, and a positive blood
culture result may help guide therapy, especially if empiric antibiotics are started and
abscess fluid culture yields no growth.2,6
• Culture specimen from any other suspected focus of infection should also be collected,
as this may also give clues for possible distant sources.14

Imaging Studies

• CT imaging of the brain (with and without contrast) is the most readily available study for
establishing diagnosis of brain abscess in the ED.
o Early in the course, abscess appears as a low-density, irregular zone that does
not enhance in the presence of intravenous contrast (early cerebritis).
o Classically, as the disease progresses, a distinctive "ring enhancement" appears
on contrast-enhanced CT, as the abscess wall thickens.
o Rarely, a well-organized abscess wall fails to generate such ring enhancement.
Such false-negative results should not have an impact on ED care or disposition;
they have more implications for inpatient care, where the timing of surgical
intervention may be dictated by response to preliminary intravenous antibiotics
and subsequent organization of the abscess wall.32
• CT is generally sufficient to make the preliminary diagnosis, which mandates
neurosurgical consultation and admission to the hospital.2,3,6
• However, MRI is increasingly being used for further evaluation.
o MRI is more sensitive in detecting early cerebritis.2
o Posterior fossa lesions may not be identified on CT scan and may require MRI to
make the critical diagnosis.2,4
o A ring-enhancing lesion on CT scan may give rise to a differential diagnosis
including abscess versus primary tumor or metastasis. Gadolinium-enhanced
MRI is helpful in characterizing these lesions. On diffusion-weighted imaging,
pyogenic abscesses have a hyperintense signal, whereas nonpyogenic lesions
will have a hypointense or mixed signal. Although not readily available in the
emergency department, proton magnetic resonance spectroscopy may also be
used to differentiate abscesses.33,34,35,36

See Brain, Abscess for images.

Other Tests

• Ultrasonography: As ultrasonography is becoming widely used in the emergency

department, bedside ocular ultrasonography may be performed to assess for increased
intracranial pressure.37

Procedures
 • Lumbar puncture (LP)
o LP results are generally not helpful in the diagnosis of brain abscess. Performing
this procedure in the emergency department is generally indicated only in cases
highly suspicious for bacterial meningitis, with a careful balance between any
potential change in management and the risk of CNS herniation.4,14
o The suspicion of brain abscess, presence of any focal neurologic finding, or of
papilledema is an absolute indication for CT imaging prior to LP.38
• In cases where LP had been performed, the findings were nonspecific and cultures were
rarely positive.2,39
• Abscess aspiration: Culture of the abscess fluid is the most important microbiological
study to ensure appropriate targeted therapy. As a result, urgent or emergent
neurosurgical consultation is necessary.

Treatment

Prehospital Care
Rapid transport is the key component of prehospital care for suspected intracranial abscess.

Emergency Department Care

• The initial evaluation is dictated by the severity of the patient's condition.

• Emergent intubation using a cerebroprotective rapid sequence induction regimen is often
necessary in patients with obtundation, inability to protect the airway, and suspected
herniation.
• Stable patients whose presentation suggests the diagnosis should undergo rapid
neuroimaging after initial evaluation.2,3,9 Close monitoring of neurologic status is essential
and having at least one nurse or advanced provider in attendance while the patient is
undergoing imaging is probably advisable.
• Antibiotics should be administered as early as possible in the patient's course in the ED.
These may be given prior to imaging in cases where the diagnosis is very strongly
suspected.14
• Seizures should be treated aggressively to decrease the risk of sustained increases in
intracranial pressure. Prophylactic anticonvulsants are often used given the relatively
high frequency of seizures in this population.3

Consultations

• Once the diagnosis is clear, immediate neurosurgical consultation is mandatory.2,3

• Infectious disease consultation may be necessary to optimize antibiotic therapy,
especially in immunocompromised hosts.2,4
• Neurology consultation is helpful in guiding both immediate and long-term management.
• Consultation with dental/oral-maxillofacial surgeons or otolaryngologists may be helpful if
the primary focus of infection is odontogenic or otorhinogenic, respectively, for co-
treatment and eradication of the primary source.40,41

Medication
Selection of appropriate antimicrobials with adequate CNS penetration and coverage of typical
anaerobic and aerobic organisms is critical in controlling infection and preventing complications.
In the early phase of abscess formation, cerebritis, patients may respond to antibiotic therapy
alone.5,9

However, in almost all cases, definitive treatment of brain abscess requires surgical drainage.2,3

Since seizures are a frequent complication of brain abscess, anticonvulsants for seizure
prophylaxis are often recommended at the initial time of diagnosis and for a prolonged period of
time, often greater than 1 year.3,9

Antibiotics
In the ED, empirical regimens of antibiotic therapy are the first-line pharmacologic treatment of
brain abscess based on presumed source:3

• Direct extension from sinuses, teeth, middle ear - Penicillin G + metronidazole + third-
generation cephalosporin
• Hematogenous spread or penetrating trauma - Nafcillin + metronidazole + third-
generation cephalosporin
• Postoperative - Vancomycin (concern for MRSA) + ceftazidime or cefepime (concern
for Pseudomonas)
• No predisposing factor - Metronidazole + vancomycin + third-generation cephalosporin

Imipenem or meropenem can also be used for broad-spectrum coverage with equal or better cure
rates compared to a standard regimen of cefotaxime and metronidazole, but imipenem has been
associated with seizures in patients with brain abscess.4

Additional targeted therapy may also be initiated in suspected fungal or protozoan infections,
especially in immunocompromised patients.2,42

Ceftriaxone (Rocephin)

Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy

against gram-positive organisms; higher efficacy against resistant organisms. Bactericidal activity
results from inhibiting cell wall synthesis by binding to one or more penicillin-binding proteins.
Exerts antimicrobial effect by interfering with synthesis of peptidoglycan, a major structural
component of bacterial cell wall. Bacteria eventually lyse due to the ongoing activity of cell wall
autolytic enzymes while cell wall assembly is arrested.
Highly stable in presence of beta-lactamases, both penicillinase and cephalosporinase, of gram-
negative and gram-positive bacteria.

• Dosing
• Interactions
• Contraindications
• Precautions
Adult

2 g IV q12-24h, max 4 g/d

Pediatric

100 mg/kg/d IV divided q12h

Cefepime (Maxipime)

Fourth-generation cephalosporin. Gram-negative coverage comparable to ceftazidime but has

better gram-positive coverage (comparable to ceftriaxone). Covers Pseudomonas.

• Dosing
• Interactions
• Contraindications
• Precautions
Adult

2 g IV q8-12h

Pediatric

Neonates: 30 mg/kg IV q12h

>2 months: 50 mg/kg IV q8h (max 2 g/dose)

Imipenem and cilastatin (Primaxin)

For treatment of multiple organism infections in which other agents do not have wide spectrum
coverage or are contraindicated due to potential for toxicity.

• Dosing
• Interactions
• Contraindications
• Precautions
Adult

500-750 mg IV q6h; in healthy young adults with excellent renal function, doses of 1 g q6h may
be necessary (max dose: 4 g/d)

Pediatric

Infants >3 months and children <12 years: 15-25 mg/kg/dose IV q6h
Fully susceptible organisms: Not to exceed 2 g/d
Infections with moderately susceptible organisms: Not to exceed 4 g/d
>12 years: Administer as in adults

Meropenem (Merrem IV)

Bactericidal broad-spectrum carbapenem antibiotic that inhibits cell-wall synthesis. Effective

against most gram-positive and gram-negative bacteria. Has slightly increased activity against
gram-negatives and slightly decreased activity against staphylococci and streptococci compared
with imipenem.
 • Dosing
• Interactions
• Contraindications
• Precautions
Adult

1-2 g IV q8h

Pediatric

<3 months: Not established

>3 months: 40 mg/kg IV q8h (max dose 2 g/dose)

Penicillin G (Pfizerpen)

May be used as first-line regimen for empiric treatment of brain abscess in ED. Provides
coverage for anaerobes and streptococci. Penetrates well into abscess cavity.

• Dosing
• Interactions
• Contraindications
• Precautions
Adult

6 million U IV q6h

Pediatric

<14 kg (30 lb): 600,000 U IV q6h

14-27 kg (30-60 lb): 900,000-1,200,000 U IV q6h
>27 kg (>60 lb): Administer as in adults

Metronidazole (Flagyl)

First line. Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa.
Has proved especially effective in otogenic brain abscesses.

• Dosing
• Interactions
• Contraindications
• Precautions
Adult

500-750 mg IV q6h

Pediatric

30 mg/kg/d IV

Cefotaxime (Claforan)
First line. Covers streptococci, staphylococci, and Haemophilus and Enterobacter species. This
third-generation cephalosporin has broad gram-negative spectrum, lower efficacy against gram-
positive organisms, and higher efficacy against resistant organisms than earlier generation
cephalosporins. Arrests bacteria cell wall synthesis and inhibits bacterial growth by binding to 1 or
more penicillin-binding proteins.

• Dosing
• Interactions
• Contraindications
• Precautions
Adult
2g IV q4-6h

Pediatric
Neonates: 50-200 mg/kg/d IV
Infants and children: 200 mg/kg/d IV divided into q6h-q8h

Nafcillin (Unipen)

Treats infections caused by penicillinase-producing staphylococci. Used to initiate therapy when

penicillin G-resistant staphylococcal infection suspected. Do not use for treatment of penicillin G-
susceptible staphylococci. Use parenteral therapy initially in severe infections. Very severe
infections may require very high doses. Change to oral therapy as condition improves. Because
of occasional occurrence of thrombophlebitis associated with parenteral route (particularly in
elderly persons) administer parenterally only for short term (24-48 h) and change to oral route if
clinically possible.

• Dosing
• Interactions
• Contraindications
• Precautions
Adult
2g IV q4h

Pediatric
Neonates:
1200-2000 g, <7 days: 50 mg/kg/d IV divided q12h
>2000 g and <7 days or 1200-2000g and >7 days: 75 mg/kg/d IV divided q8h
>2000 g, >7 days: 100-140 mg/kg/d IV divided q6h
Children: 200 mg/kg/d in divided doses q4-6h

Vancomycin (Vancocin)

Replaces nafcillin in both penicillin-allergic patients and those in whom MRSA is suspected as
etiologic agent. Potent antibiotic directed against gram-positive organisms and active against
enterococci. Also useful in treating septicemia and skin structure infections. Adjust dose as
needed in patients with renal impairment. Check trough level after third dose (30 min prior to next
dose) to avoid toxicity.

• Dosing
• Interactions
• Contraindications
• Precautions
Adult
1 g IV q12h or loading dose of 15 mg/kg IV q8-12h
Dose for peaks 25-40 mcg/mL, troughs 5-10 mcg/mL

Pediatric
60 mg/kg/d IV in divided doses q6h

Ceftazidime (Fortaz, Ceptaz)

Add to empiric regimens if pseudomonads are suspected. Third-generation cephalosporin that

has broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher
efficacy against resistant organisms than many agents. Arrests bacteria cell wall synthesis and
inhibits bacterial growth by binding to 1 or more penicillin-binding proteins.

• Dosing
• Interactions
• Contraindications
• Precautions
Adult
6 g/d IV

Pediatric
Not established

Corticosteroids
Use of steroids is controversial. The anti-inflammatory effects of steroid therapy can decrease
cerebral edema, reducing intracranial pressure (ICP). These benefits are offset somewhat by the
fact that steroid use decreases antibiotic penetration into the abscess and may slow
encapsulation of the abscess site. Therefore, many authors recommend steroids only in cases of
massive cerebral edema with impending herniation.3,14

Dexamethasone (Decadron, Dexasone)

Corticosteroid of choice for reducing ICP. Used in treatment of inflammatory diseases. May
decrease inflammation by suppressing migration of polymorphonuclear leukocytes and reversing
increased capillary permeability.

• Dosing
• Interactions
 • Contraindications
• Precautions
Adult

Loading dose: 10-12 mg IV

Maintenance dose: 4 mg IV q6h

Pediatric

Loading dose: 1-2 mg/kg/dose IV once

Maintenance dose: 1-1.5 mg/kg/d IV
Not to exceed 16 mg/d divided q4-6h for 5 d; taper dose for 5 d and discontinue

Follow-up

Further Inpatient Care

• A combined medical and surgical approach is used for most brain abscesses to eradicate
the invasive organism.12
• Duration of antibiotic treatment is unclear and is dictated by clinical response.
Traditionally 6-8 weeks of intravenous antibiotics has been used followed by oral
antibiotics for another 4-8 weeks to prevent relapse.2,4,9,43 One series reported clinical
resolution in some patients with only 2 weeks of intravenous therapy,2 indicating that
some patients may not need extended parenteral treatment.
• Surgery is the only way to precisely isolate the causative organism and tailor antibiotic
therapy. One study concluded that antibiotic pretreatment for up to 10 days does not alter
culture positivity of intracerebral specimen.14 However, other series show that up to 40%
of abscess cultures may be negative,8 presumably due to early empiric antimicrobial
therapy.
• At present, most neurosurgeons use nonoperative management (ie, prolonged courses of
parenteral antibiotics) only in rare cases. Indications may include patients with the
following:2,3,44
o Single abscess smaller than 2 cm
o Multiple abscesses
o Critical illness at a terminal stage
o Abscess in an inaccessible location
• Surgical options include aspiration, incision and drainage, or excision depending on the
location, size, number of sites, and other characteristics of the abscess as well as the
patient's clinical status.2,3,45 The specific choice of surgical technique is less important than
the basic principle of removing the pathogen.3
• Many abscesses that were once inoperable can now be reached by stereotactic
aspiration guided by precision mapping of the lesion's location by CT or
MRI.3,43 Stereotactic aspiration is widely preferred to open craniotomy because it is
minimally invasive, has low morbidity/mortality, and allows rapid drainage.2,6Reports of
magnetic resonance fluoroscopy to guide aspiration also exist.46
• Some interest exists in the possible role of hyperbaric oxygen as an adjunct therapy to
the initial phase of treatment with intravenous antibiotics. Reports in children47 and in
adults48 suggest that such adjunct therapy may reduce the length of inpatient stay by
 decreasing the duration of antibiotics needed for clinical improvement; however, the
number of cases studied to date is small.

Further Outpatient Care

Interval CT scans are recommended for inpatients and outpatients to follow up for complications
and resolution of abscess,3,4 as there is a risk of abscess reaccumulation or failure to resolve in
some cases requiring reaspiration.2,12

Transfer
Lack of neurosurgical availability is an indication for transfer to a medical center that has such
support.

Complications
Complications of brain abscess may include the following:

• Uncal or tonsillar herniation due to increased intracranial pressure (ICP)30

• Rupture of abscess into ventricles or subarachnoid space is a complication. This is often
lethal. High-risk features for this complication include an abscess that is deep seated,
multiloculated, and/or close to the ventricular wall.49
• Recurrence of abscess2
• Long-term neurologic sequelae in up to 50% of patients (ie, hemiparesis, seizures)4,6,14,31

Prognosis

• Survival rates for brain abscess are excellent.12

• Characteristics associated with an excellent prognosis include the following:
o Young age14
o Absence of severe neurologic defect on initial presentation14,50
o Absence of neurologic deterioration during initial workup14,50
o Absence of comorbid disease14,50
• Worse prognosis of brain abscess is associated with the following:
o Signs of herniation on initial presentation (Mortality rate exceeds 50%.14 )
o Altered sensorium at time of presentation8
o Extent of brain lesion on radiology (ie, increased size, critical location, more
lesions, increasing edema/midline shift)51
o Short duration of symptom-onset before diagnosis4
o Delay in surgical intervention45
o Gram-negative infection52
o Nocardial abscess (Mortality rate is 3 times that of bacterial abscess and can
reach fatality rates as high as 50% in immunocompromised patients.19 )

Patient Education
For excellent patient education resources, visit eMedicine's Infections Center, Brain and Nervous
System Center, and Brain and Nervous System Center. Also, see eMedicine's patient education
articles Brain Infection,Antibiotics, and Brain Infection.
Miscellaneous

Medicolegal Pitfalls

• Failure to obtain emergency neuroimaging in patients with headache and new neurologic
defect
• Failure to accurately identify and distinguish brain abscess from other ring enhancing
lesions and begin immediate treatment
• Discharging a patient without explaining a new neurologic finding
• Failure to heed family concerns about unusual patient behavior when other symptoms
suggestive of brain abscess are present.